Central catecholamines are known to be involved in the ability of animals to respond to stressful events. Immunological stimuli, such as endotoxin and plant lectins activate the host response to fight invading antigens. This is accompanied by neuroendocrine changes analogous to the response to external, consciously perceived threats. We have studied the effects of these immunological stimuli and the products of activated macrophages, interleukin (IL-1) and tumor necrosis factor (TNF) on turnover of catecholamines in brains in both rats and mice. The mechanism(s) by which cytokines exert their central effect(s) is unknown. Using microdialysis, we examined the direct effect of IL-1, IL-6 and muramul dipeptide on hypothalamic catecholamine release in anesthetized rats. No direct norepinephrine releasing effect was observed. Further, anesthesia markedly attenuated the increased turnover in central catecholamines observed following intraperitoneal administration of either LPS or IL-1. These data suggest that the increase in catecholamine turnover observed in CNS following these agents is an indirect effect mediated by some peripheral phenomenon such as pain or inflammation resulting in sympathetic activation.